内科学教学课件：Nephrotic Syndrome

NephroticSyndromeLearningobjectivesClinicalmanifestation,pathologyandtreatmentofnephroticsyndromePathophysiologyofnephroticsyndromeComplicationsofnephroticsyndromeOutlineDefinitionPathophysiologyPathologyandclinicalmanifestationComplicationsDiagnosisanddifferentialdiagnosisTreatmentMr.O19yearsolduniversitystudentNoticedfoamingurineduringthepast3-4weeksPuffingface,swellingfeetfor1weekHadgain9kgbodyweightShoestootighttowearSlightlyfatigueandSOB,otherwisenormalFigure1.Nephroticedema.Figure2.Nephroticedema.Diagnosis:Proteinuria:>3.5g/dHypoalbuminemia:SAlb<30g/LEdemaHyperlipidemiaPro++++WhatwillyoudoforMr.O?Whatwillyoudo?Urineroutine24hurinaryproteinKidneyfunctionLiverfunctionandserumalbuminLipids……Let’sgobacktoMr.OUrineprotein++++,RBC(-),WBC(-)24hurinaryprotein7.8gNormalkidneyandLiverfunctionSerumalbumin20g/LTotalcholesterol10.2mmol/LMr.OwasdiagnosedwithnephroticsyndromeProteinuria(albuminuria)Figure3.HypoalbuminemiaAlbuminImmunoglobulinsMetalbindingproteinsErythropoietinurinarylossTransferrinComplementdeficiencyCoagulationcomponentsMechanismsleadingto

nephrotichypoalbuminemiaHyperlipidemiaMostNSpatientshaveelevatedlevelsoftotalandlow-densitylipoprotein(LDL)cholesterolwithlowornormalhigh-densitylipoprotein(HDL)cholesterol.Lipoprotein(a)[Lp(a)]levelsareelevatedaswell.Nephroticpatientsoftenhaveahypercoagulablestateandarepredisposedtodeepveinthrombophlebitis,pulmonaryemboli,andrenalveinthrombosis.MechanismsofHyperlipidemiaIncreasedhepaticsynthesisofLDL,VLDLandlipoprotein(a)inresponsetohypoalbuminemiaUrinarylossofHDLEnzymaticchangeswithabnormallipidbiosythesisanddegradationEdemaTwodifferentmajormechanisms:Intheclassictheory,proteinurialeadstohypoalbuminemia,alowplasmaoncoticpressure,andintravascularvolumedepletion.Subequentunderperfusionofthekidneystimulatestheprimingofsodium-retentivehormonalsystemssuchastheRASaxis,causingincreasedrenalsodiumandvolumeretention.EdemaHowmanypathologicaltypesinnephroticsyndrome?ForMr.O,whichpathologicaltypeisthemostlikely?PathologyMinimalchangedisease(MCD)Mesangialproliferativeglomerulonephritis(MsPGN)Membranoproliferativeglomerulonephritis(MPGN)Membranousnephropathy(MN)Focalsegmentalglomerulosclerosis(FsGs)Minimalchangedisease

(MCD)Epidemiology:

ItisthemostcommoncauseofNSinchildren,accountingfor80-90%ofyoungpatientswithNS,whileonly10-20%inadults.Thereappearstobeamalepreponderance,especiallyinchildren,inwhomthemale-to-femaleratiois2~3:1Minimalchangedisease

(MCD)Pathology

NoglomerularlesionsbylightmicroscopyNostainingwithantibodiesspecificforimmunoglobulinsorcomplementcomponentsEffacementofvisceralepithelialcellfootprocessesFigure5a.Pathologyofglomerulardisease.Lightmicroscopy.(a)Normalglomerulus;minimalchangedisease.Minimalchangedisease

(MCD)Clinicalmanifestations:ThecardinalclinicalfeatureofMCDinchildrenistherelativelysuddenonsetofproteinuriaanddevelopmentoftheNS.Hematuria,hypertensionandimpairedkidneyfunctionarenotcommon.Mesangialproliferativeglomerulonephritis(MsPGN)Epidemiology:

ItisacommonreasonofNSinourcountry,accountingfor30%ofprimarynephroticsyndrome,higherthanthoseinwestern.Mesangialproliferativeglomerulonephritis(MsPGN)Pathology

DiffuseproliferationofmesangialcellsandECMPositivestainingwithIgA,IgG,IgMorC3inmesangialareaDensedepositsinmesangialareaMesangialproliferativeglomerulonephritis(MsPGN)Clinicalmanifestations:50%hasinfectionbeforeonsetofkidneydisease.Non-IgAN:50%withNS,70%withhematuriaIgAN:15%withNS,almostallwithhematuriaMembranoproliferativeglomerulonephritis(MPGN)Epidemiology:

Itisaccountingfor10-20%ofprimarynephroticsyndromepatientsinourcountry.Membranoproliferativeglomerulonephritis(MPGN)Pathology

SeverediffuseproliferationofmesangialcellsandECM,demonstratingdoublingandmorecomplexreplicationofglomerularbasementmembranesPeripheralgranulartobandlikestainingforC3andIgGDensedepositsinmesangialsubendothelialareaFigure8.PathologyofmembranoproliferativeglomerulonephritistypeI.(a)Lightmicroscopyshowsahypercellularglomeruluswithaccentuatedlobulararchitectureandasmallcellularcrescent(methenaminesilver).Membranoproliferativeglomerulonephritis(MPGN)Clinicalmanifestations:50-60%presentasanephroticsyndrome.AlmostallpatientswithhematuriaEarlyonsetofimpairmentofkidneyfunction,hypertension,anemiaProgressivedisease(10yearrenalsurvivalrate50%)Membranousnephropathy

(MN)EpidemiologyMembranousnephropathyistheleadingcauseforprimarynephroticsyndromeinadults.Membranousnephropathy

(MN)PathologySubepithelialimmunecomplex;projectionsofbasementmembrane;depositssurroundedbybasementmembrane;thickenedbasementmembraneIgGandC3positivestainingincapillaryFigure7a.EarlyMN:aglomerulusfromapatientwithseverenephroticsyndromeandearlyMN,exhibitingnormalarchitectureandperipheralcapillarybasementmembranesofnormalthickness(Silver–methenamine×400).Figure7bmorphologicallyadvancedMNFigure7c.MorphologicallymoreadvancedMN(samepatientasin(b))Membranousnephropathy

(MN)Clinicalmanifestations:80%withNS30%withmicroscopichematuriaRenalveinthrombosisseenin40-50%patientsFocalsegmentalglomerulosclerosis(FsGs)EpidemiologyOverthepasttwodecades,therehasbeenanincreasedincidenceofFSGS,accountingfor10%inourcountry.SomecasesdevelopedfromMCD.Focalsegmentalglomerulosclerosis(FsGs)PathologyItischaracterizedbyfocalandsegmentalglomerularsclerosisNonscleroticglomeruliandsegmentsusuallyhavenostainingforimmunoglobulinsorcomplement.Figure6.Lightmicroscopicappearancesinfocalsegmentalglomerulosclerosis.Segmentalscarswithcapsularadhesionsinotherwisenormalglomeruli.Focalsegmentalglomerulosclerosis(FsGs)Clinicalmanifestations:NS¾withhematuriaHypertensionandrenalfunctiondecliningarecommonMr.OMinimalchangedisease(MCD)Mesangialproliferativeglomerulonephritis(MsPGN)Membranoproliferativeglomerulonephritis(MPGN)Membranousnephropathy(MN)Focalsegmentalglomerulosclerosis(FsGs)Mr.OMinimalchangedisease(MCD)Mesangialproliferativeglomerulonephritis(MsPGN)Membranoproliferativeglomerulonephritis(MPGN)Membranousnephropathy(MN)Focalsegmentalglomerulosclerosis(FsGs)ComplicationsInfectionmalnutritionlossofimmunoglobulinscorticosteroidsThrombosiscoagulation,corticosteroids,PLTactivityComplicationsAcuterenalfailure(ARF)HypoalbuminemiaHypovolemiapre-renalazotemiaProteinmalnutritionanddyslipidemiaDiagnosisDiagnosis:NS?Primaryorsecondary?Pathologicaltype?Complications?

DifferentialdiagnosisTypeChildrenYoungpatientsMiddleandoldagePrimaryMCDMsPGNMNMCDFsGsMPGNSecondaryHenoch-Schonlein

purpuraLupusnephritisDiabeticnephropathyHepatitisBassociatedGNHenoch-Schonlein

purpuraAmyloidosisLupusnephritisHepatitisBassociatedGNMyelomaLymphomaandothertumorLet’sgobacktoMr.OWhatwillyoudotoexcludesecondaryNS?WhatwillyoudotoexcludesecondaryNS?MedicalhistoryandphysicalexaminationBloodsugarHepatitisvirusds-DNA,ANA,ENA,Complements,ESRTumormarkersUltrasound,X-ray……Let’sgobacktoMr.OMr.Owasfinallydiagnosedwithprimarynephroticsyndrome,MCDHowtotreathim?TreatmentSupportcareRest;restrictproteinintake(0.8-1.0g/kg/d);lowsaltintake(<3g/d)DiuretictherapyDiminishingproteinuria:ACEIandARBTreatmentImmunosupressivetreatmentCorticosteroid

Principleofusingsteroids:startwithenoughdose(1mg/kg/d),slowdosetapering(10%every2-3weeks),long-termmaintenance.

Becarefulofsideeffectsofcorticosteroid.TreatmentCytotoxicdrugs:

Cyclophosphamide(CTX)Cyclosporine(CsA)Mycophenolatemofetil(MMF)TreatmentMinimalchangedisease:sensitivetosteroids;singledrug;reuse